Murine model of invasive pulmonary Aspergillosis: Follow-up of tissue injury, fungal burden and mortality with distinct elastase production strains

Abstract

To study invasive pulmonary Aspergillosis (IPA), we depleted neutrophils in mice using the monoclonal antibody anti-Gr-1/Ly-6G. Immunocompetent and neutropenic mice were infected via intratracheal with conidia of Aspergillus fumigatus clinical isolates, characterized as either higher or lower elastase producers. Neutropenic animals exhibited 100% mortality in 5 days, for both strains, and were observed survival curves overlapped, lungs with angioinvasion, rupture of bronchial and vascular walls, associated with exuberance of conidia filamentation. The immunocompetent animals infected with the lower elastase producer strain presented with upregulated inflammatory processes, and a lack of conidia filamentation in the tissue. The fungal burden in the lungs was not different in the immunocompetent and neutropenic groups. These findings confirm the protective role of neutrophils against A. fumigatus and suggest that the fungal elastinolytic activity is not a critical virulence factor but may be involved in tissue injury.

Keywords: Aspergillus fumigatus; Elastase; Experimental IPA; Fungal burden; Gr-1/Ly-6G monoclonal antibodies; Histopathological studies.